title: Neurodegeneration in Parkinson's disease: interactions of oxidative stress, tryptophan catabolites and depression with mitochondria and sirtuins.
abstract: The biological underpinnings to the etiology and course of neurodegeneration in Parkinson's disease are an area of extensive research that has yet to produce an early biological marker or disease-slowing or preventative treatment. Recent conceptualizations of Parkinson's disease have integrated immuno-inflammation and oxidative and nitrosative stress occurring in depression, somatization and peripheral inflammation into the course of Parkinson's disease. We review the data showing the importance of immuno-inflammatory processes and oxidative and nitrosative stress in such classically conceived 'comorbidities', suggesting that lifetime, prodromal and concurrent depression and somatization may be intricately involved in the etiology and course of Parkinson's disease, rather than psychiatric comorbidities. This produces a longer term developmental perspective of Parkinson's disease, which incorporates tryptophan catabolites (TRYCATs), lipid peroxidation, sirtuins, cyclic adenosine monophosphate, aryl hydrocarbon receptor, and circadian genes. This integrates wider bodies of data pertaining to neuronal loss in Parkinson's disease, emphasizing how these interact with susceptibility genes to drive changes in mitochondria, blood-brain barrier permeability and intercellular signalling. We review this data here in the context of neurodegeneration in Parkinson's disease and to the future directions indicated for slowing disease progression.
authors.affiliation: CRC, Rm 30, 57 Laurel St., Glasgow, G11 7QT, Scotland, UK, anderson.george@rocketmail.com.
authors.forename: George
authors.initials: G
authors.lastname: Anderson
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003863:Depression / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D037761:Sirtuins / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D014364:Tryptophan; D037761:Sirtuins